Effect of GSL inhibitor (CB-839) on growth, proliferation, survival, and metabolism of MCL cells. (A) Results of MTT conversion assay with the depicted 6 patient-derived MCL cell lines after 72-hour incubation in vehicle (DMSO) or various concentrations of CB-839, ranging from 0 to 1000 nM. (B) Cell cycle phases with compartmentalization (R3, sub G0/G1; R4, G0/G1; R5, S; R6, M) detected after 48-hour exposure of the MCL cell populations to CB-839 or the inhibitor’s (control) medium. (C) Apoptotic cell death identified by a DNA fragmentation (TUNEL) assay after 72-hour MCL cell exposure to CB-839 vs control medium. (D) Key metabolites in MCL-SL cells. Metabolites affected by the cell treatment with CB-839, identified by Liquid Chromatography-Mass Spectrometry (LC-MS) and metabolome-targeting bioinformatics, are highlighted by green background; the CB-839–induced changes in the MCL-SL identified signals are displayed in the associated graphs (black columns, control; and red columns, CB-839). α-KG, α-ketoglutarate; CoA, Coenzyme A; DMSO, dimethyl sulfoxide; GABA, gamma-aminobutyric acid; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; TCA, tricarboxylic acid; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.

Effect of GSL inhibitor (CB-839) on growth, proliferation, survival, and metabolism of MCL cells. (A) Results of MTT conversion assay with the depicted 6 patient-derived MCL cell lines after 72-hour incubation in vehicle (DMSO) or various concentrations of CB-839, ranging from 0 to 1000 nM. (B) Cell cycle phases with compartmentalization (R3, sub G0/G1; R4, G0/G1; R5, S; R6, M) detected after 48-hour exposure of the MCL cell populations to CB-839 or the inhibitor’s (control) medium. (C) Apoptotic cell death identified by a DNA fragmentation (TUNEL) assay after 72-hour MCL cell exposure to CB-839 vs control medium. (D) Key metabolites in MCL-SL cells. Metabolites affected by the cell treatment with CB-839, identified by Liquid Chromatography-Mass Spectrometry (LC-MS) and metabolome-targeting bioinformatics, are highlighted by green background; the CB-839–induced changes in the MCL-SL identified signals are displayed in the associated graphs (black columns, control; and red columns, CB-839). α-KG, α-ketoglutarate; CoA, Coenzyme A; DMSO, dimethyl sulfoxide; GABA, gamma-aminobutyric acid; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; TCA, tricarboxylic acid; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.

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